How to disable the "Save Over" popup
To the best of my knowledge, this cannot be changed. Here are a few workarounds that might be helpful however.
Use a script
If you use the command bpy.ops.wm.save_mainfile() and register a shortcut, you would just need to do a normal save once (for Blender to get the path) and after that, use CtrlShift + Y as I have done in the script below to save without any popups. (You can also change this if you want, see the commented line).
import bpy

class SaveWithoutPrompt(bpy.types.Operator):
    bl_idname = &quot;object.save_without_prompt&quot;
    bl_label = &quot;Save without prompt&quot;

    def execute(self, context):
        bpy.ops.wm.save_mainfile()
        return {'FINISHED'}

def menu_func(self, context):
    self.layout.operator(SaveWithoutPrompt.bl_idname)

addon_kmaps = []

def register():
    bpy.utils.register_class(SaveWithoutPrompt)

    wm = bpy.context.window_manager
    km = wm.keyconfigs.addon.keymaps.new(name='Object Mode', space_type='EMPTY')
    # change the shortcut here..
    kmi = km.keymap_items.new(SaveWithoutPrompt.bl_idname, 'Y', 'PRESS', ctrl=True, shift=True)
    addon_kmaps.append(km)

def unregister():
    bpy.utils.unregister_class(SaveWithoutPrompt)
    bpy.types.VIEW3D_MT_object.remove(menu_func)

    wm = bpy.context.window_manager
    for km in addon_kmaps:
        wm.keyconfigs.addon.kmaps.remove(km)
    del addon_kmaps[:]

if __name__ == &quot;__main__&quot;:
    register()


Set the autosave feature to save more often

You could have Blender save a copy of the file you are working on every minute. This runs in the background so no popups. You can find this feature under the File tab in your User Preferences.
Related, Blender saves a new file every time